Twenty-five white men with rapid eye movements (REM) sleep behavior disorder, but without narcolepsy, underwent HLA class II antigen typing: 84% (N=21) were DQwl (DQB1*05,06) positive (28% [N=7] were DR2 positive); DQB1*0501 (N=9) and DQB1*0602 (N=7) were the most common phenotypes. The 84% DQwl rate in men with REM sleep behavior disorder was significantly greater (p=0.015) than the 56% DQwl rate found in a local white comparison group (N=66), and was greater than the 39 to 66% DQwl rates published for 12 white groups (N=40-418/group). Thus, another disorder of REM sleep dysregulation (besides narcolepsy) appears to be strongly associated with specific HLA class II genes.