To calculate the sensitivity and specificity of multifocal electroretinography (mfERG) in detection of chloroquine and hydroxychloroquine retinal toxicity, 120 eyes of 63 patients were evaluated using the currently recommended diagnostic tests. The results were compared to those of 54 eyes of 28 control subjects. The sensitivity and specificity of mfERG relative to the combination of automated visual fields and optical coherence tomography (the reference test) were calculated to be 87% and 86.5% respectively. However, analysis of the “false positive” cases proved that mfERG was more sensitive than the reference test and the actual sensitivity and specificity values were higher than the results of this study. Reduction of mfERG amplitude was a strong and reliable sign of early retinal toxicity and was correlated with the cumulative dose of hydroxychloroquine. This correlation was not observed with the reference test quantitative values.