Idarubicin was conjugated to anti-Ly-2.1 and anti-L3T4 monoclonal antibodies. These conjugates were used to investigate their effects on skin graft survival in mice. Several donor and recepient combinations were used so that the effect of individual or mixtures of conjugates on class I and class II antigenic differences, as well as multiple H-2 and non-H-2 antigenic differences could be studied. Ida-anti-Ly-2.1 prolonged skin grafts for class I antigenic differences. A mixture of Ida-anti-L3T4 and Ida-anti-Ly-2.1 was more effective than either conjugate alone in prolonging the survival of skin grafts with class II antigenic differences. However, idarubicin conjugates alone or in combination were unable to prolong graft survival when multiple H-2 and non-H-2 differences existed. In all models free idarubicin or unconjugated monoclonal antibody did not prolong the skin grafts.