Summary Maturity-onset diabetes of the young (MODY) is a heterogeneous subtype of non-insulin-dependent diabetes mellitus characterised by early onset, autosomal dominant inheritance and a primary defect in insulin secretion. To date five MODY genes have been identified: hepatocyte nuclear factor-4 alpha (HNF-4/MODY1/TCF14) on chromosome 20 q, glucokinase (GCK/MODY2) on chromosome 7 p, hepatocyte nuclear factor-1 alpha (HNF-1/MODY3/TCF1) on chromosome 12 q, insulin promoter factor-1 (IPF1/MODY4) on chromosome 13 q and hepatocyte nuclear factor-1 beta (HNF-1/MODY5/TCF2) on chromosome 17cen-q. We have screened the HNF-4, HNF-1 and HNF-1 genes in members of 18 MODY kindreds who tested negative for glucokinase mutations. Five missense (G31D, R159W, A161T, R200W, R271W), one substitution at the splice donor site of intron 5 (IVS5nt + 2TA) and one deletion mutation (P379fsdelT) were found in the HNF-1 gene, but no MODY-associated mutations were found in the HNF-4 and HNF-1 genes. Of 67 French MODY families that we have now studied, 42 (63 %) have mutations in the glucokinase gene, 14 (21 %) have mutations in the HNF-1 gene, and 11 (16 %) have no mutations in the HNF-4, IPF1 and HNF-1 genes. Eleven families do not have mutations in the five known MODY genes suggesting that there is at least one additionnal locus that can cause MODY. [Diabetologia (1998) 41: 10171023]