Previous research has documented that exposure to a drug reduces the ability of the drug to support subsequent flavor-aversion learning. The four experiments reported here examined the hypothesis that this drug-preexposure effect is due to associative interference from environmental stimuli associated with the drug effects during preexposure. When distinctive environmental stimuli (confinement in a black compartment) were present during drug preexposure, these stimuli significantly disrupted subsequent flavor-aversion learning. Furthermore, flavor conditioning was not significantly disrupted when drug preexposure occurred in the absence of salient environmental stimuli or when the previously conditioned environmental stimuli were extinguished prior to flavor conditioning. It is significant, and in contrast to other published research, that flavor conditioning was not disrupted when the distinctive cues paired with the drug during preexposure were absent at the time of the flavor-drug pairing. These results are thus consistent with results from conventional studies of stimulus blocking and suggest that associative processes can play a major role in the drug-preexposure effect.