The role of spinal cord mu opioid receptor expressing dorsal horn neurons in morphine analgesia is not clearly understood. Using lumbar intrathecal (i.t.) injections of the targeted toxin dermorphin-saporin to selectively destroy these cells, we sought to determine the effect of this lesion on the antinociceptive activity of systemic and i.t. morphine on the hotplate test. We examined the antinociceptive effects of morphine across a range of stimulus intensities (44, 47 & 52 C) in order to assess responses mediated by C or A-delta thermal nociceptors: 1 - Sixteen Sprague Dawley (S-D) male rats were injected with 500ng dermorphin-saporin or PBS intrathecally. Baseline hotplate responses were monitored for three weeks then systemic morphine dose response curves (0, 2.5, 5, &10 mg/kg, s.c.) were performed. 2 - Twelve Long Evans female rats were surgically implanted with indwelling lumbar i.t. catheters, underwent baseline hotplate testing for 7 days, had i.t. morphine dose response curves performed at 44 & 52 C seven days before and eight days after dermorphin-saporin injections. We measured latencies to the first lick or guard response (all temperatures) and the cumulative durations and amounts of licking and guarding events (44 and 47 C). Spinal cord sections from each rat were stained for MOR1 and MOR1C using standard immunoperoxidase techniques on adjacent 40 μm sections from the L4 spinal segment. Baseline responses to noxious heat did not change after i.t. dermorphin-saporin. The antinociceptive activity of systemic morphine was attenuated in dermorphin-saporin treated rats at 44 & 47C; this effect was not significant on the 52 C hotplate and greatest on the 44 C hotplate. Dermorphin-saporin-induced attenuated the antinociceptive effects of intrathecal morphine more than systemic morphine. We conclude that dorsal horn MOR expressing neurons are necessary for morphine to exert full antinociceptive and analgesic effects.