The purpose of this study was to determine which delta (delta) opioid receptor subtype, delta 1 or delta 2, was involved in producing the antinociceptive action of heroin and 6-monacetylmorphine (MAM) in Swiss Webster mice. Previous work from this laboratory established that heroin and MAM, given intracerebroventricularly (i.c.v.) in Swiss Webster mice, produce antinociception through activation of supraspinal delta receptors. Naltrindole, but not naloxone or nor-binaltorphimine, antagonizes the inhibitory action of heroin and MAM in the tail-flick test. Recent literature documents the occurrence of subtypes of the delta opioid receptor and the availability of selective antagonists. 7-Benzylidenenaltrexone (BNTX) antagonizes the antinociception induced by delta 1 receptor agonists without affecting that induced by delta 2 receptor agonists. Naltriben (NTB) selectively inhibits delta 2- but not delta 1-induced antinociception. In the present study BNTX and NTB were administered i.c.v. with heroin and MAM to determine the delta receptor subtype responsible for inhibition of the tail-flick response in Swiss Webster mice. The ED50 for heroin-induced antinociception was increased 19-fold by BNTX and was not altered by NTB administration. On the other hand, the ED50 value of MAM was increased 3-fold by NTB and was not altered by BNTX administration. These results suggest that heroin activated supraspinal delta 1 receptors and MAM acted on supraspinal delta 2 receptors to produce antinociception in Swiss Webster mice.