The Flinders Sensitive Line (FSL) rat, a genetic animal model of depression, was cross-bred with its normal control, the Flinders Resistant Line (FRL) rat, in order to investigate the relationship between cholinergic sensitivity, the selected variable, and two apparent genetically correlated variables, serotonergic sensitivity and swim test immobility. Cross-breeding established F1, F2 and back-cross progeny, with at least 20 rats of each sex for each group. Cholinergic sensitivity was assessed as the hypothermic response to oxotremorine (0.2 mg/kg) in 30 day old rats. Serotonergic sensitivity was assessed as the hypothermic response to 8-OH-DPAT, a serotonin (5-HT)-1A agonist, in 35-40 day old rats. Immobility was assessed as the time spent immobile in a 5 min swim test in 60-70 day old rats. For each variable, there were highly significant group differences, with the parental FSL and FRL groups being at the extremes. The segregating populations tended to be intermediate between the parental lines and were generally significantly different from both FSL and FRL groups. However, the crosses more closely resembled the FRL parent for only the cholinergic responses, the distributions for 8-OH-DPAT and immobility suggesting predominantly additive genetics. Statistical analyses with chi square to compare response distributions and regression to quantify the association between variables in the segregating populations confirmed that cholinergic sensitivity was different from serotonergic sensitivity and immobility, which were significantly correlated with each other.(ABSTRACT TRUNCATED AT 250 WORDS)