A mutation within the glucagon receptor gene (GRG) at codon 40 (Gly40Ser) was reported to be associated with non-insulin-dependent diabetes mellitus (NIDDM) in France and Sardinia. Since the frequency of the mutation, about 5% in the French and 8% in the Sardinian group was higher than that of any of the candidate gene mutations described so far, it appeared to be relevant to determine the prevalence within different populations. While a single mutation has not been found recently either in a Japanese, a Finnish or a Dutch cohort, but only in a British study in 2.2% of NIDDM patients, in this study we investigated the association of this mutation with NIDDM in 104 German patients by polymerase chain reaction-restriction fragment length polymorphism analysis (PCR-RFLP). None of the German NIDDM patients had a Gly40Ser mutation. The results indicate that the mutation plays little role in susceptibility to NIDDM in this German region, and also indicate the genetic heterogeneity in NIDDM, and further emphasize the importance of studies in different ethnic groups.