Experimental studies in rodents demonstrate evidence of immunosuppressive effects of dietary exposure to DDT [2,2-bis((italic)p(/italic)-chlorophenyl)-1,1,1-trichloroethane], but human data pertaining to immunomodulating effects of DDT exposure are limited. In this study we examined the association between the persistent organochlorine breakdown product 1,1-dichloro-2,2,bis(p-chlorophenyl)ethylene p,p'-DDE) and immunologic measures using blood samples in a relatively highly exposed population of farmers in the United States. Levels of serum immunoglobulin A (IgA) and IgG and the prevalence of antinuclear antibodies in relation to plasma p,p'-DDE levels were evaluated in samples from 137 African-American male farmers (30-88 years of age; median, 64 years). Participants were recruited through black churches in four rural counties in eastern North Carolina. Data collection included a telephone interview pertaining to farming practices and health history, and one blood sample was collected from each participant. Linear and logistic regression, adjusting for age, cholesterol, triglycerides, smoking status, and years of any kind of pesticide use, was used to assess the association between immunologic parameters and plasma levels of p,p'-DDE. The median plasma p,p'-DDE concentration was 7.7 microg/L (range, 0.6-77.4 microg/L). There was no association between p,p'-DDE and IgA in any of the models. IgG levels decreased with increasing p,p'-DDE levels, with a statistically significant decrease of approximately 50% in the highest two categories of exposure (greater than or equal to 6.0 microg/L) compared with values of < 3.0 microg/L. Sixteen (12%) were positive for antinuclear antibodies. The prevalence of antinuclear antibodies was somewhat elevated in the highest category of p,p'-DDE exposure (odds ratio, 1.9; 95% confidence interval, 0.32-11.3; for > or = 12.0 microg/L compared with < 3.0 microg/L p,p'-DDE), but this difference was not statistically significant. These analyses provide evidence that p,p'-DDE modulates immune responses in humans.