Twelve cats were implanted with cortical and depth electrodes. After they recovered from the operation, visual evoked responses (VERs) were recorded at 20 min following saline and methadone (0.5, 1, 2, 3, 4 mg/kg) administered IP in a semi-random order to each cat. Four other cats were similarly drugged and plasma was obtained for radioimmunoassay of methadone content. At the three lowest dose levels behavioral excitation and salivation were evident in some cats, while their VER configuration remained essentially unaltered and plasma methadone was barely measurable. Following the 3 and 4 mg/kg doses plasma methadone concentration increased dramatically, behavioral excitation and salivation were evident in most cats and VERs were reliably altered. The VER alterations, consisting of amplitude attenuation and a decrease in some latencies, were restricted to secondary VER components occurring between 50 and 100 msec despite the animals' extreme behavioral excitation. These results suggest that the reticular formation is not a principal site of the drug's effect.