ANOVA; duration, (F(2,60)=29.19, p<0.0001); genotype (F(3,60)=3.07, p=0.0439; interaction between duration and genotype, (F(3,60)=0.1143, p=0.951, n.s.; Bonferroni multiple comparisons between N2 and other genotypes, t(11)=0.0824–1.94, p>0.05, n.s., n=6). The behavioral consequences of exc-4 and exl-1 mutations are therefore likely to be related to changes in the pharmacodynamic responses to ethanol as opposed to altered pharmacokinetics of the drug. These studies indicate that both Clic orthologues in C. elegans influence ethanol-related behavior. The effects of mutations in exc-4 and exl-1 on initial sensitivity and acute tolerance in worms, however, are wholly distinct and suggest that different Clic genes could play distinct roles in ethanol-related behavior.