The objective of this study was to identify DNA sequence variation in the UCP gene and to investigate its relationship with some obesity phenotypes. Two studies were carried out: (1) association study in unrelated subjects, and (2) sib-pair linkage analysis study in brothers and sisters. The subjects were 261 individuals from the Québec Family Study (123 parents and 138 offsprings from 64 families). The following were measured: Body mass index, percent body fat (measured by hydrostatic weighing), and subcutaneous fat (estimated by the sum of 6 skinfolds) were measured in 1978-81 and again 12 years later. Resting metabolic rate (RMR) was measured only in 1989-93. Genetic analyses were performed using Southern blotting technique and a human UCP genomic probe. (1) A BcII restriction fragment length polymorphism was identified with two alleles of 8.3 and 4.5 kb in length, and respective frequencies of 0.28 and 0.72. (2) In unrelated adults from the parental generation, a cross-sectional analysis of the 1989-93 data showed no difference in body fat and RMR between the UCP genotypes. No significant difference for the absolute changes in body fat over the 12-year period among the UCP genotypes was observed. However, a higher frequency (P < 0.05) of the 8.3-kb allele was found in high gainers compared to low gainers (i.e., above and below the median value) for percent body fat over the 12-year period. (3) No evidence of linkage between any of the obesity phenotypes and the UCP BcII marker was found. For the first time, the presence of DNA polymorphism in the human UCP gene is reported. Although, no significant association and linkage were found between the UCP BcII gene marker and body fat in the cohort of the Quebec Family Study, a higher frequency of the 8.3-kb allele was found in individuals who gained more body fat over time.