Superfused interrenal tissue of Sarotherodon aureus responded to ACTH with increased release of cortisol. The response to ACTH of interrenal tissue taken from fish treated with the organochlorine insecticide 1,1-dichloro-2-(o-chlorophenyl)-2-(p-chlorophenyl) ethane (o,p-DDD; 50 mg/kg) in vivo was almost totally abolished. Lower doses were less effective. The response was also suppressed by exposure in vitro of the interrenal tissue to the organochlorine; there seemed to be a dose-response to o,p-DDD over the range of 0.023 to 1 mg/l. Also 1,1-dichloro-2,2-bis (p-chlorophenyl) ethylene (p,p'-DDE) was effective in suppressing the response to ACTH at concentrations of 50--150 mg/l; 1,1,1-trichloro-2,2-bis (p-chlorophenyl) ethane (p,p'-DDT) or the polychlorinated biphenyl, Aroclor 1254, were ineffective at 50 mg/l. No suppressive effect of o,p-DDD on output of cortisol could be detected in superfusion when N6,O2'-dibutyryl cyclic AMP (20 mmol/L) was substituted for ACTH. This may indicate that the interference of o,p-DDD with the interrenal response to ACTH results from an interruption in the generation of cyclic AMP.