The Knops, McCoy, Swain-Langley and York antigens have recently been identified as being on complement receptor type 1 (CRI, CD35, C3b/C4b receptor). We examined the relationship between CR1 expression and the reactivity of the CRl-related blood group antigens with their specific antibodies. RBC from donors of selected phenotypes were tested by hemagglutination using two monoclonal antibodies to CR1, as well as anti-Kn^a, -McC^a, -S1^a, -‘Kn/McC’ and -Yk^a. Monoclonal antibodies 3D9 and E11 required ~250 and ~400 CR1/RBC to obtain a positive reaction. Agglutination of antigen-positive cells by human polyclonal antisera was related to the CR1/RBC: thus, cells expressing 20-100 CR1/RBC were negative and included the previously designated null phenotypes for this collection, 100-150 were weak or negative, and >200 were usually positive. One RBC sample carried Yk^a on the 190,000 dalton (A or F allele), but not the 220,000 dalton (B or S allele) variant of CR1, and gave inconsistent reactions with Yk^a antisera. These data provide an explanation for certain of the serologic characteristics of the CR1-related blood group antigen system.