The preference characteristics for ethanol of four different strains of rats were determined in a two-choice situation by offering water and ethanol in a concentration which was increased from 3 to 30% over a 12-day test sequence. Using stereotaxic procedures, 50 μg 5,6-dihydroxytryptamine (5,6-DHT), 200 μg 6-hydroxydopamine (6-OHDA) or 100 μg 5,7-dihydroxytryptamine (5,7-DHT) were then injected acutely into the lateral cerebral ventricle in a 20 μl volume. Rats of the Sprague-Dawley strain increased their ehthanol preference following the lesioning of the serotonergic system by 5,6-DHT, whereas similar destruction of catecholaminergic neurons by 6-OHDA markedly suppressed ethanol intake; Long-Evans rats displayed a similar trend in ethanol drinking patterns. However, animals of the Holtzman strain manifested the increased drinking after 5,6-DHT, but showed no suppression of drinking following 6-OHDA. The preference of rats of the Wistar strain was unaffected by 5,6-DHT but attenuated by 6-OHDA. 5,7-DHT had little or no effect on ethanol comsumption in any of these strains. These findings thus suggest that genetic factor are an important determinant in an animal's response to a drug that affects 5-HT or NE systems in the brain, particularly when ethanol selection is investigated.