To study the stimulatory capacity of HLA-DR beta III in the mixed lymphocyte culture (MLC) assay, an MLC matrix between 13 Dw18 homozygous typing cells (HTCs) was analysed. Six of these HTCs were positive for the HLA-DR beta III allele LB-Q1 as defined by T cell clones. Seven HTCs were positive for LB-Q4. The MLC responses between Dw18 HTCs, matched for LB-Q, were significantly lower than the responses between the mismatched combinations. Considering the fact that HLA-DP can induce proliferation in MLC, we then analysed the DP matched and mismatched combinations separately. The influence of HLA-DR beta III mismatches was in our experiments comparable to the influence of mismatches for HLA-DP. Surprisingly, 15 out of 22 DR beta III and DP matched combinations still showed positive MLC reactions.