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To investigate polymorphisms in the atrial natriuretic peptide gene of Aftican Americans at intron two (Hpall) and exon three ( Scal)The allele frequency of the Hpall mutation was 25% in the hypertensive group (n=60) compared with only 3.4% in normotensive individuals (n=44, P<0.0001). The genotype heterozygote for the present mutation was much more common among those with hypertension (50 versus 6.8%, P<0.0001). The groups were no different for the Scal site alone, although the two mutations were present together more often in the hypertensive group. The Hpall mutation was associated with hypertension in this typically salt-sensitive population.