C4 genotyping was performed in 38 unrelated patients with systemic lupus erythematosus (SLE) aged 2-16 years at onset. Null alleles were found in 68% of patients. Ten patients had one null allele at the C4A locus and 11 others had one null allele at the C4B locus. One patient was homozygous for C4A*Q0, 2 homozygous for C4B*Q0 and 1 heterozygous C4A*Q0/B*Q0. The last patient was C4A*Q0B*Q0/B*Q0. Three patients, being heterozygous C2 deficient, had thus a combined C2 and C4 deficiency. A significant increase in C4 null alleles in SLE patients has been reported by different authors who have suggested that the C4 null alleles confer susceptibility to SLE. However, when considering only the 20 patients of French descent, no differences in gene frequencies were found between this group and the French population. Disease patterns were compared in patients with or without null C4. Renal involvement was more frequent in the C4A*Q0 or C4A*Q0/C4A*Q0 patients than in the patients without null C4 (9/11 vs 3/12). These data suggest that differences between these results and those of others might be due to clinical heterogeneity of the disease, as exemplified by the frequency of renal involvement in the different groups. In susceptible individuals the absence of one C4A gene product may predispose the patient to renal involvement.