Uncoupling protein-1 (UCP1) is uniquely expressed in brown adipose tissue (BAT) and of major importance for the tissues thermogenic capacity. This study was undertaken to detect variants in the UCP1 gene by single strand conformational polymorphism (SSCP) analysis and subsequent sequencing, and determine their potential association with obesity. Four variants predicting for amino acid substitutions were detected, of which Arg40Trp (exon 1) and Lys257Arg (exon 5) were rare mutations. In contrast, the allele frequency of a polymorphism in exon 2 predicting for an Ala64Thr substitution was 8.2% in a cohort of 293 obese children and adolescents compared to 4.1% in 134 lean individuals, while the allele frequency of a Met229Leu variant (exon 5) was not markedly different between the obese (10.4%) and lean (12.0%) study groups. Although one of the identified polymorphisms tends to have a higher frequency in obese than in lean subjects, variants of the UCP1 gene do not seem to contribute significantly to the development of early-onset obesity in the German population.