Most studies on hormonally active agents or endocrine disruptors have been limited to polychlorinated biphenyls and dioxins. In this paper, we report results of in vitro studies on the effects of alkylphenolic compounds, namely, n-pentylphenol, n-hexylphenol, n-heptylphenol, n-octylphenol, and n-nonylphenol, on the injury rate, survival, and acetylcholinesterase activity of the rat pheochromocytoma cell line PC12. Results using the lactate dehydrogenase cytotoxicity assay to determine cell injury rate reveal that the alkylphenols mentioned did not induce cell necrosis beyond 30%, even at concentrations as high as 300 muM in a 15-min incubation period. Exposing the cells to alkylphenols for 4 hr and testing for DNA fragmentation showed that nonylphenol and octylphenol also did not induce apoptosis, even at concentrations as high as 500 and 100 muM, respectively. However, incubating the cells with the alkylphenols for 24 hr significantly inhibited acetylcholinesterase activity at concentrations as low as 0.8 muM, with n-octylphenol showing the most significant effect Since it is believed that human exposure to nonylphenol from drinking water is around 0.7 mug day(-1) and that these compounds can accumulate in adipose tissue, this finding may implicate alkylphenols in neurological and behavioral disturbances in both animals and humans.