This study was performed to clarify the apparent differences in the cellular substrates mediating the discriminative stimulus effects of morphine and cyclazocine. Squirrel monkeys trained to discriminate between i.m. injections of saline and either morphine (3.0 mg/kg) or cyclazocine (0.1 mg/kg) in a two-choice avoidance paradigm were tested for stimulus generalization to ethylketocyclazocine and SKF 10,047, proposed agonists of receptors mediating the effects of cyclazocine. Both drugs completely mimicked the stimulus effects of cyclazocine but not those of morphine. Naltrexone (0.3 mg/kg) produced a 3-fold shift to the right of the cyclazocine dose-response curve but did not completely block the cyclazocine-like stimulus effects of either SKF 10,047 or ethylketocyclazocine. SKF 10,047 was a competitive antagonist at the receptors mediating the stimulus effects of morphine. These data are consistent with a multiple opiate receptor model, and provide further evidence that the stimulus effects of morphine and cyclazocine are subserved by different cellular substrates.