Mixed leukocyte culture studies on 120 families, including 120 HL-A haplo-identical siblings and 210 HL-A identical siblings, were analyzed for unusual patterns for reactivity. Three discrepant reactions were noted in which cells from HL-A-identical siblings showed strong mutual stimulation. These data provide an estimate of 0.0065 as the recombination frequency between the HL-A-B and HL-A-D regions of the major histocompatibility chromosome in man. When combined with previous data, the value is 0.0068 with a 95% confidence interval of 0.0022-0.0158.