There are marked interethnic differences in beta 1-adrenoceptor-mediated responsiveness, with sensitivity decreased in African-Americans and increased in Chinese compared with Caucasians. Therefore, the frequency of a common naturally occurring polymorphism of the human beta 1-adrenoceptor gene (Arg389Gly), which has functional importance in vitro, was determined in 194 African-Americans, 316 Caucasian-Americans, 221 Hispanic-Americans and 142 Chinese. African-Americans were found to have a significantly lower frequency of the Arg389 allele than the other three ethnic groups (all P < 0.01). In the populations studied, the order of the distribution of the Arg389 allele was: Chinese (74%) > Caucasians (72%) > Hispanics (67%) > African-Americans (58%). To determine the functional significance of the Arg389Gly beta 1-adrenoceptor polymorphism, in-vivo heart rate responses to exercise were compared in healthy subjects homozygous for the Arg (n = 9) and Gly (n = 8) alleles. Heart rate response to exercise was not affected by genotype (P = 0.4). Although ethnic differences in the frequency of the beta 1-adrenoceptor Arg389Gly polymorphism exist, the polymorphism does not appear to have functional significance in healthy subjects and therefore may not contribute to ethnic differences in response to drugs acting through the beta 1-adrenoceptor.