Previously, we found that cancer patients using a pharmacokinetically based patient-controlled intravenous infusion system (PKPCA) to regulate their own morphine infusion rates achieved more relief from oral mucositis pain than similar patients using morphine by bolus-dose PCA. In this study, we employed the PKPCA system to compare efficacy and side-effect intensities of 2 mu-selective opioid analgesics, alfentanil and morphine, in bone marrow transplant (BMT) patients self-administering the drugs to relieve pain from oral mucositis. Patients using morphine by PKPCA obtained more pain relief than patients regulating their own alfentanil infusions during the first 4 days of continuous opioid infusion therapy. Side-effect intensities did not differ between the 2 study groups. In contrast to patients using morphine for 4-14 days, those receiving alfentanil by PKPCA required unexpectedly high plasma concentrations of the drug to obtain equivalent pain relief. Our results indicate that either the relative potencies of these 2 mu-selective opioids differ from previous estimates or analgesic tolerance developed to alfentanil but not to morphine. We conclude that alfentanil has similar efficacy in control of prolonged pain in BMT patients, but the utility of alfentanil in long-term pain management may be limited by relatively rapid tolerance onset.