There have been conflicting reports as to whether the mean sperm count in some men has diminished over the last 50 years. The downward trend has been suggested to coincide with an increase in exposure to estrogen-like compounds. These estrogenic substances are ubiquitous in the environment. We have examined the effect of such substances (diethylstilbestrol, beta-estradiol, daidzein, genestein, and nonylphenyl) in the single cell gel electrophoresis assay (Comet assay) in human sperm and compared responses with those from human peripheral lymphocytes in the same donor and in peripheral lymphocytes from a female donor. In addition, effects from the estrogens have been compared to those from known reprotoxins and genotoxins. These include lead sulfate, nitrate and acetate, dibromochloropropane, ethylene glycol monoethyl ether, 1,2-epoxybutene, and 1,2,3,4-diepoxybutane. All compounds produced positive responses, but ethylene glycol monoethyl ether only produced positive responses in sperm cells in the male and not in peripheral lymphocytes, and similarly the phytoestrogens (genistein, daidzein) were less responsive in the peripheral lymphocytes in the male than in the sperm. This may be due to greater sensitivity of sperm cells because of their lack of repair. However, since damage was generally seen over a similar dose range, a one-to-one ratio of somatic and germ cell damage was observed and has implications for man for risk assessment purposes. (C) 1997 Wiley-Liss, Inc.