4-tert-Octylphenol is a non-ionic surfactant used as a detergent, emulsifier and wetting agent. It is generally accepted that it acts as a weak estrogenic substance when evaluated in in vitro and in vivo short-term screening assays. The sensitivity of animal species (mouse versus rat), strain (inbred versus outbred) has been a matter of concern when selecting assay type for testing of estrogenicity of chemicals. The present study was designed to investigate whether the choice of different animal strain, could affect the outcomes of studies. Fischer and Wistar adult male rats were exposed to vehicle or 400 mg/kg bw of 4-tert-octylphenol administrated orally by gavage. Estradiol benzoate, at a dose of 40 microg/kg bw, was used as positive control agent. Treatment with estradiol benzoate decreased serum levels of testosterone, LH, FSH, inhibin and increased prolactin. Additionally, estradiol benzoate decreased the weight of all investigated reproductive organs, decreased sperm production and increased seminiferous tubular degeneration in both strains. More progressive effects on testis weight and histopathology were observed in the Fischer rats. Oral administration of octylphenol at 400 mg/kg bw to both rat strains increased prolactin levels but had no effect on LH, FSH, testosterone or inhibin. In the octylphenol-treated Fischer rats the weights of the seminal vesicles and the levator ani/bulbocavernosus muscle were significantly decreased, whereas only the levator ani/bulbocavernosus muscle was affected in Wistar rats. The weights of all other reproductive organs and sperm count were unaffected. It is concluded that there might be an organ specific difference in sensitivity between the two strains with the Fischer rat being the most sensitive rat model as demonstrated mainly by the more progressive effects on testis weight and histopathology in estradiol benzoate-treated Fischer rats but also by the decrease in seminal vesicle weight in octylphenol-treated rats.