The effect of nicotine injected intrathecally (i.t.) on the inhibition of the tail-flick response induced by morphine, beta-endorphin, D-Pen2,5-enkephalin (DPDPE), or [(trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl] benzeocetamide)] (U50,488H) administered i.t. was studied in ICR mice. The i.t. injection of nicotine alone at doses from 1 to 12 microg produced only a minimal inhibition of the tail-flick response. Morphine (0.2 microg), beta-endorphin (0.1 microg), DPDPE (0.5 microg) or U50,488H (6 microg) caused only slight inhibition of the tail-flick response. Nicotine injected i.t. dose dependently enhanced the inhibition of the tail-flick response induced by i.t. administered morphine (0.2 microg). However, i.t. injected nicotine at the same doses was not effective in enhancing the inhibition of the tail-flick response induced by beta-endorphin, DPDPE, or U50,488H administered i.t. Our results suggest that stimulating nicotinic receptors located in the spinal cord may enhance the antinociception induced by morphine administered spinally. However, the activation of nicotinic receptors at the spinal level may not be involved in modulating the antinociception induced by beta-endorphin, DPDPE, and U50,488H administered spinally.