The calcium channel blocker diltiazem is often included in post-transplant regimens in combination with other immunosuppressive drugs such as cyclosporin A (CyA). It is primarily used because of its antinephrotoxic and antihypertensive effects, so that undesirable side effects induced by the immunosuppressive therapy can be reduced. Its alleged ability to induce direct immunosuppression may explain the encouraging results from its clinical use and would appear to encourage a much wider use of this drug. The present study shows the effect of diltiazem on the human in vitro alloresponse when used alone or in combination with cyclosporin A (CyA) and methylprednisolone (MP). The results show that, when administered alone, diltiazem exerts a suppressive effect, but only at high, non-therapeutic doses. Interestingly, in combination with CyA or MP, diltiazem enhances the suppressive effect of these two drugs on in vitro alloresponses at lower doses. This additional effect of diltiazem may contribute to better graft survival in clinical transplantation.