Previous investigations have established the production of specific epididymal proteins (SEP) in the rat which become attached to the sperm surface as these cells pass along the duct. The present study is concerned with the regulation of SEP synthesis by androgens. For this purpose, we determined the concentrations of SEP and protein DE, one of its main components (40%), during sexual maturation, after castration with and without androgen administration, and after ligation of the efferent ductuli in rats. SEP were first detectable at 25 days of age and attained adult values at 60-90 days of age. Protein DE behaved similarly. Castration of the adult rat led to a decrease in SEP and DE concentrations. The fall was more rapid and marked in the caput than in the caudal segments. SEP synthesis seemed to stop promptly after castration; the different rates of decrease of SEP in caput and cauda may reflect different rates of exit of spermatozoa from those segments. SEP and DE concentrations in castrated rats were increased by the administration of testosterone (100 micrograms/day). The SEP concentration was increased after 4 days and restored to control values after 11 days of treatment. Testosterone and 5 alpha-dihydrotestosterone were equipotent in inducing SEP and DE synthesis, while 5 alpha-androstandiols were less potent. The effects of androgens were significantly reduced by the simultaneous administration of cyproterone acetate. We propose that SEP is a suitable marker for following the action of androgens in the epididymis.