Methionine-enkephalin (ME) released from superfused slices of rat corpus striatum was estimated by radioimmunoassay (RIA). The basal release of 2.5 +/- 0.2 pmol/g/min (0.15% of content per min) was increased approximately 3-fold upon exposure of tissue to 30 mM K+ for 5 min. This increase in release was not observed in the absence of Ca2+. Both morphine (10(-5) M) and (-)-naloxone (10(-5) and 10(-6) M) significantly depressed the release of ME evoked by 30 mM K+ did not alter basal release. The (+)-isomer of naloxone, which lacks opiate antagonist activity, did not affect basal or evoked release. A consistent depression of release was not observed when 47 mM K+ was used to evoke the release of ME. The issue of whether a feedback mechanism controls the release of ME from the striatum cannot be resolved until it is known whether the effect of morphine and naloxone on ME release are mediated by opiate or non-opiate mechanisms.