Male and female rats of two lines psychogenetically selected for bipolar extremes in shuttle box avoidance were evaluated for tremor, salivation, chromodacryoorhea, and hypothermia following treatment with the muscarinic cholinergic agonist oxotremorine. Roman Low-Avoidance (RLA/Verh) rats exhibited more pronounced oxotremorine-induced tremor, chromodacryorrhea, and hypothermia than Roman High-Avoidance (RHA/Verh) rats. There was a sex difference only for a chromodacryorrhea response, with females exhibiting a greater response following oxotremorine than males. In a subsequent experiment using female rats of both rat lines, it was demonstrated that pre-treatment with the cholinergic antagonist scopolamine blocked oxotremorine-induced tremor, salivation and chromodacryorrhea responses in both rat lines and reduced the hypothermic effect observed in RLA/Verh rats (but not the much weaker hypothermia found in RHA/Verh rats) after oxotremorine injection. Pretreatment with the peripherally active cholinergic antagonist methscopolamine significantly reduced oxotremorine-induced salivation and chromocacryorrhea and somewhat decreased tremor and hypothermic responses in both rat lines. These results stand in contrast to the results of earlier research in which RHA/Verh rats exhibited greater behavioral depression in a tunnel maze than RLA/Verh rats following cholinergic manipulations. In view of evidence that these rat lines do not differ in number of muscarinic brain receptors, the present results may be due to genetic differences in other aspects of cholinergic neurotransmitter function, differences in the function of other neurochemical systems, or differences in the absorption, distribution, or metabolism of oxotremorine.