To examine the role of the alpha 2-adrenoceptor gene in the development of genetic hypertensive rats, we tested Dahl salt sensitive (S) and resistant rats (R) for the presence of a restriction fragment length polymorphism (RFLP) in that gene. An RFLP was found between the S and R rats with a human kidney cDNA alpha 2-adrenoceptor probe (alpha 2-C4) and Msp I restriction endonuclease. The alpha 2-C4 probe detected two alleles, S and R, of 3.0 and 2.8 kb in size. The two strains of rats were each homozygous for their corresponding allele. The inheritance of the alleles was investigated by crossbreeding S and R rats and subsequent brother/sister mating of F1 rats. Two hundred and fifteen F2 rats were produced by breeding 14 pairs of F1 rats. An atypical distribution of alpha 2-adrenoceptor genotypes was observed. We found a reduced number of the SS genotype in both males and females of the F2 generation. To investigate the mechanism of this distorted alpha 2-adrenoceptor genotype distribution in the F2 rats of S and R cross, we backcrossed the F1 rats to their S and R parents. The litter size and gender distribution were counted for each breeding colony. Analysis by chi-square test showed that there was no sex difference among the backcrosses. Also, there was no significant decrease in litter size. This excludes the possibilities of fetal demise of S homozygotes and intrauterine selection. Therefore the deficiency of SS genotype may be due to gene recombination or may not be due to the alpha 2-adrenoceptor gene itself, but to the effect of other genes closely linked to the alpha 2-adrenoceptor.