The potential modulating influence of fluoxetine (FLU) on the effects of cocaine (COG) on vigilance task performance was explored. Rats were trained in a discrete-trial task in which pressing one of two levers was reinforced by food, with the correct lever indicated by the position of a briefly illuminated light. Tests with FLU (2.5, 5.0, and 10.0 mg/kg) revealed no significant effects of FLU on mean choice accuracy, log choice reaction time, or number of omission trials; however, 10.0 mg/kg FLU did produce a small but reliable increase in mean log food retrieval latency. The effects of COC (1.25, 2.5 and 10.0 mg/kg) were then assessed following pretreatment with saline or FLU (2.5 and 10.0 mg/kg). COC increased mean choice accuracy, with maximal performance enhancement occurring with choice reaction time was decreased by all three doses of COC, although there was considerable within-subject variability at the 10.0 mg/kg dose of COC. Pretreatment with FLU reversed both of these performance-enhancing effects of COC in a dose-dependent fashion. Log food retrieval latency was not significantly affected by the lower doses of COC and was significantly increased by the 10.0 mg/kg dose of COG. FLU and COC appeared to interact in an additive fashion with this measure. The number of omission trials per session was significantly increased by 10.0 mg/kg COC-an effect that was not significantly altered by FLU pretreatment. These results support previous studies indicating that acute FLU exposure can reduce many of COC's properties that may contribute to COC's efficacy as a positive reinforcer. Copyright (C) 1997 Elsevier Science Inc.