National Institutes of Health (NIH) heterogeneous stock (HS) rats were obtained and genetically selected for either larger (HI line) or smaller (LO line) hypothermic responses to the selective serotonin-1A (5-HT1A) agonist 8-hydroxy-2-(di-N-propylamino)tetralin (8-OH-DPAT). A randomly bred (RA) control line was also bred in parallel. There was a rapid response to selection, with HI and LO S1 progeny already showing significantly different hypothermic responses to DPAT. The data for the S3 progeny indicated that selection was proceeding in both directions, with the hypothermic responses of the LO line being about 0.5 degrees C less than that of the RA line (p < 0.01) and the hypothermic response of the HI line being about 0.7 degrees C greater (p < 0.01). The selected lines also differed in their hypothermic responses to the cholinergic agonist oxotremorine, but these differences did not change with further selection. These findings indicate that selection for 5-HT1A sensitivity may occur quite rapidly and that changes in muscarinic sensitivity do not parallel those changes in serotonergic sensitivity.