Earlier human health surveys, cytogenic and molecular biologic studies by the investigators suggested that offspring of pesticide appliers might have excess reproductive risk expressed as birth anomalies and/or reduced fertility. To begin to evaluate this hypothesis, 4,935 births to 34,772 state licensed private pesticide appliers in Minnesota occurring between 1989 and 1992 were linked to the Minnesota state birth registry containing 210,723 live births in this time frame. Significant increases were found in all birth anomalies, and in specific categories of birth anomalies. Examination of pesticide use showed that the greatest increase occurred in the region of the state with highest use of chlorophenoxy herbicides/fungicides. The region is a well defined area of the Red River Valley. The male/female sex ratio of anomalies was significantly increased in appliers residing in the region. In the five counties with the highest chlorophenoxy herbicide/fungicide use, the number of births to appliers was significantly reduced. The present study is designed to address in detail the issues of reduced fertility and birth anomalies in three of the five counties with the highest chlorophenoxy herbicide/fungicide use. To achieve this goal, an integrated survey and laboratory based investigation focused on fertility is proposed. The survey will include 2,333 appliers and their spouses. These data will characterize individual and regional pesticide use, and provide preliminary information on fertility. Laboratory studies will focus on male mediated cases of infertility and birth anomalies. Endocrine disruption, spermatotoxicity, sperm and somatic cell aneuploidy, frequency of chromosome constitutional abnormalities and chromosomal hot spots associated with pesticide exposure will be examined. Preliminary laboratory data are consistent and suggest that endocrine disruption and chromosomal effects in the male appliers may be important factors in the apparent decrease in fertility.