PIP: A community-wide (Rochester, Minnesota), case-control study of the incidence severity, trends, and possible etiologic factors, both environmental and genetic, of hypospadias, between 1940-1970, is presented. Of 13,776 live male births, 113 cases 8.2/1000) of hypospadias were found. There was no significant variation in the rates by 5-year periods and no cyclic pattern noted. In 7 instances, 2 brothers were affected, and in 4 families, the father was also affected. There was no difference between index and control mothers with respect to drug usage. Hydroxyprogesterone caproate, i.m., had been given to 4 index mothers and 1 control mother, 3 index mothers had received thyroid therapy during the first trimester, 1 index mother and 4 control mothers had received meclizine, 4 control mothers had received estrogen, and 9 index mothers and 5 control mothers had taken oral contraceptives (combination) within 9 months of their last menstrual period. There was a larger proportion of testicular anomalies which might have adversely affected spermatogenesis and semen quality among index fathers than among control fathers. These data suggest a multifactorial etiology of hypospadias fitting a polygenic model.