The collagen type Ialpha1 Sp1 (ColIA1) polymorphism has been associated with reduced bone mineral density (BMD) and increased prevalence of osteoporosis. This study examines associations of the ColIA1 genotype with BMD and 5-year rates of change in BMD in elderly men and women. The 243 subjects, aged 65 years and older, were participants in two consecutive studies lasting a total of 5-years. BMD of the total body, femoral neck, and lumbar spine were made by dual-energy X-ray absorptiometry (DXA). The distribution of the genotypes (155 in the SS genotype, 79 in Ss, and 9 in ss) was proportionately similar to those reported by others. Baseline BMD did not differ significantly at any skeletal site. Unadjusted 5-year percent changes in BMD differed significantly by genotype only at the total body (P = 0.009), where the change was -0.29+/-0.21 (SEM) in the SS genotype, -0.60+/-0.25 in the Ss genotype, and -3.01+/-0.72 in the ss genotype. This 9.4% increase in bone loss of the ss genotype relative to the SS genotype was reduced to an 8.9% increase after adjustment for sex, age, weight, and supplementation group. Results at the femoral neck were directionally similar, but not statistically significant. No effect of genotype on change in spine BMD was observed. In conclusion, bone loss from the total body was significantly greater in elderly men and women who were homozygous for the s allele compared with heterozygotes and SS homozygotes. This finding suggests a possible explanation for the association of the ColIA1 polymorphism with increased rates of osteoporotic fracture, but should be interpreted with caution because of the small number of subjects in the unfavorable ss genotype.