The acute nervous system toxicity of organophosphate (OP) pesticides is well described. However, the reported long-term effects of OP pesticides on the nervous system are inconsistent. This inconsistency may be due to imprecise estimates of pesticide exposure, variability of central nervous system (CNS) and peripheral nervous system (PNS) assessment, small samples, and poor control of confounding. The primary goal of this research was to examine the association between long-term OP pesticide use on CNS and PNS function among pesticide applicators. An additional goal was to examine the association between high pesticide exposure events (HPEEs), which typically do not result in acute toxicity, and CNS function. Study participants were recruited from among applicators enrolled in the Agricultural Health Study (AHS) in Iowa and North Carolina. In 2006-2008, 701 male pesticide applicators completed a battery of neurobehavioral (NB) and neurological tests. Information about individual pesticide use was obtained from previous AHS interviews and a questionnaire administered during NB testing. Associations between pesticide use and neurological outcomes were estimated with linear and logistic regression models while controlling for covariates. When associations were examined between agent-specific pesticide use and nine NB tests, significantly poorer performance was observed on four tests and significantly better performance on five tests. Additionally, for some pesticides, we observed differential associations by state, suggesting that regional differences in pesticide practices may influence neurotoxicity. Overall, our results did not provide strong evidence that OP pesticide use was associated with adverse NB test performance. A history of at least one HPEE was reported by 23 percent of participants. Significant adverse associations were observed between HPEEs and two of the nine NB tests. Participants with HPEEs were, on average, 4.9 seconds slower on a test of visual scanning/processing, and 2.2 seconds slower on a test of visual scanning/motor speed. Overall, small but meaningful associations were observed between HPEEs and adverse CNS function. When associations were examined between pesticide use and PNS function, five of six neurological physical examination outcomes were associated with ever-use of one or more OP pesticides. Odds ratios ranged from 1.9 to 3.1. However, mostly null associations were observed between OP pesticide use and electrophysiological tests, hand strength, sway speed and vibrotactile threshold. This study provides some evidence that long-term exposure to OP pesticides is associated with impaired PNS function. In summary, our results suggest that exposure to a few individual OP pesticides as well as HPEEs may contribute to adverse neurological function. The observed exposure-effect associations were present after adjustment for confounding and were independent of past-diagnosed pesticide poisoning. We believe this research contributes important new evidence to an inconsistent literature. Reducing pesticide exposure and preventing HPEEs among pesticide applicators remain important public health goals.