We used amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) to document the prevalence of three mutations in the beta chain of the high-affinity IgE receptor (Fcepsilon RI-beta): I181L, V183L, and E237G in a sample of black and white asthmatic and control subjects in South Africa to determine whether these variants contribute to the enhanced IgE responses in these groups and also to determine whether the discrepancy in the prevalence of atopy in these groups could be attributed to these variants, as whites tend to be more atopic than blacks. There was a significant difference in the frequency of I181L between white asthmatics (28%) and white control subjects (3%) (p = 0.00001), and between black control subjects (16%) and white control subjects (p = 0.002); no difference in the frequency of I181L was observed between black asthmatics (22%) and black control subjects (16%). V183L was found in one black asthmatic who was also positive for I181L and E237G. There was a significant difference in the frequency of E237G between black asthmatics (20%) and white asthmatics (12%) (p = 0.05), and between control subjects (20%) and white control subjects (5%) (p = 0.003). E237G was more prevalent in blacks (20%) than in whites (8.5%) (p = 0.001). I181L might predispose to atopy in the white population, but not in the black population. The significantly higher prevalence of E237G in blacks than in whites might explain why blacks tend to have more severe asthma than whites and might offer more insight into the higher asthma mortality rate in the black population as compared with the white population.