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A number of toxicities associated with methylene chloride have been found in both human subjects and mice. However, relatively few studies have probed immunotoxicities of methylene chloride. In order to examine possible immunotoxicities or immunomodulating effects of methylene chloride, several tests of cellular immune function were performed using both human in In Vitro studies and a mouse model. Body weights and specific organ weights of thymus, spleen, liver, and kidney were normal in CD-1 mice given various concentrations of methylenechloride. However, a significantly reduced mitogenic response to phytohemagglutinin (PHA} and reduced interleukin-2 (IL-2} production was found in these methylene-chloride-treated mice. The findings in the mouse model provide additional evidence that immune suppression may be associated with exposure to methylene chloride. Splenic mononuclear cells isolated from CD-1 mice were incubated with various concentrations of methylene chloride in vitro and investigated for blastogenic response to mitogen PHA and IL-2 production. The results show no significant difference between methylene-chloride-treated cells and the cells treated with growth media. Peripheral blood mononuclear cells isolated from healthy donors were incubated with various concentrations of methylene chloride and tested for blastogenic activity, natural killer (NK) cell activity, and IL-2 production. The findings showed that the NK cell activity, the T-cell blastogenesis in response to PHA mitogen, and IL-2 production activity were not affected.