Objective To evaluate the long‐term efficacy and safety of slow oral desensitization in the management of patients with hyperuricemia and allopurinol‐induced maculopapular eruptions. Methods A retrospective evaluation of an oral desensitization regimen using gradual dosage‐escalation of allopurinol in 32 patients (30 with gout and 2 with chronic lymphocytic leukemia) whose therapy was interrupted because of a pruritic cutaneous reaction to the drug. Results Twenty‐one men and 11 women with a mean age of 63 years (range 17–83 years), a mean serum urate level of 618 μmoles/liter (range 495–750) (or, mean 10.4 mg/dl [range 8.3–12.6]), and a mean serum creatinine level of 249 μmoles/liter (range 75–753) (or, mean 2.8 mg/dl [range 0.8–8.5]) were studied. Desensitization failed in 4 patients because of unmanageable recurrent rash. Twenty‐eight patients completed the desensitization procedure to a target allopurinol dosage of 50–100 mg/day, 21 without deviation from the protocol for a mean of 30.5 days (range 21–56 days) and 7 requiring dosage adjustments because of a recurrent rash over 53.8 days (range 40–189 days). Seven of these 28 patients developed late cutaneous reactions 1–20 months postdesensitization, 4 responding to dosage modification and 3 discontinuing the drug. Twenty‐five of the 32 patients (78%) continued to take allopurinol; their mean duration of followup was 32.6 months (range 3–92 months) and the mean postdesensitization serum urate level was 318 μmoles/liter (range 187–452) (or, mean 5.3 mg/dl [range 3.0–7.5]). Conclusion The study confirms the long‐term efficacy and safety of slow oral desensitization to allopurinol in patients with maculopapular eruptions, particularly in those with gout, who cannot be treated with uricosurics or other urate‐lowering drugs. Although pruritic skin eruptions may recur both during and after desensitization, most of these cutaneous reactions can be managed by temporary withdrawal of allopurinol and dosage adjustment.