The human cytotoxic T-lymphocyte-associated protein 4 (CTLA4) gene may be a candidate susceptibility gene in multiple sclerosis (MS). In this study the distribution of the dimorphisms of exon 1 (+49 A/G) and promoter (-318 C/T) regions of the CTLA4 gene was analysed in 296 unrelated Norwegian MS patients and 271 matched controls by polymerase chain reaction and restriction fragment length polymorphism. The frequency of the exon 1 (+49) A-G genotype was increased in patients (57%) compared with controls (44%) (Pcorrected=0.01), and even more increased in patients with relapsing remitting MS (59%) (Pcorrected=0.006). No other significant differences were found between clinical subgroups of patients or between HLA-DRB1*1501, DQB1*0602-positive and negative patients and controls.