A number of previous studies have shown that the level of natural killer (NK) cell activity in humans is relatively constant for a given individual but varies widely between individuals. The factors which determine this variability are largely unknown, but genetic factors appear to be involved. In the present study it was found that Rh- normal subjects and melanoma patients had significantly higher natural cytotoxicity to target cells than Rh+ patients. This difference did not appear to be due to sensitization against Rh antigens on the target cell and may indicate that genes determining NK-cell activity are associated with those determining the expression of Rh antigens. Analysis of the survival data for Rh- and Rh+ patients did not reveal any increase in survival attributable to the higher natural cytotoxicity in Rh- patients.