Individually matched (rhesus-D) Rh-positive frozen/thawed red blood cells were used to immunize 28 Rh-negative male volunteers. The immunizing schedule consisted of a single unit (200 ml) of frozen/thawed red blood cells, followed by six monthly booster doses (0.5 to 1.0 ml) after a rest period of six months. A final response rate of 93 percent (26 of 28) was achieved. All responders had produced anti-D before the second booster injection (mean detection time 4.25 months). Retrospective analysis indicated that the final response rate and the level of anti-D response could be predicted as early as seven to eight months from the start of immunization. These findings have practical implications for deciding when to discontinue immunization. The Rh genotype of the immunizing cells did not appear to be an important factor in determining the anti-D response, and with the matching system used, antibodies other than anti-C, D, and/or E were not produced. The use of frozen/thawed red blood cells for immunization has the advantage of permitting optimum matching for undesirable red blood cell antigens and minimizing the risk of transmitting disease to the recipients.