The objective of this study was to determine if tamoxifen or an aromatase inhibitor (4-hydroxyandrostenedione; 4-OHA) affected plasma concentrations of o,p' -DDT and its metabolites, o,p'-DDD and o,p'-DDE, in mature tilapia. Male and female tilapia were injected 6 times intraperitoneally with o,p'-DDT (40 mg/kg) alone or in combination with 4-OHA (2 mg/kg) over a 12 day period. An additional group of male fish was injected with tamoxifen (5 mg/kg) plus o,p'-DDT. At the end of the treatment period, plasma samples were extracted and analyzed by GC/ECD. Females injected only with o,p'-DDT had significantly higher levels of o,p'-DDT compared with males. Interestingly, females and males treated concomitantly with o,p'-DDT and 4-OHA or tamoxifen had significantly lower concentrations of plasma o,p'-DDT (about 50%) compared with fish treated with only o,p'-DDT. These initial results suggest that an interaction between endocrine-active compounds occurs in vivo in tilapia and may involve alterations in metabolism of o,p'-DDT.