OBJECTIVE: To determine patients' knowledge of the safe use and toxicity of methotrexate (MTX) and to define educational interventions implemented by a rheumatology nurse that improved patients' understanding of MTX therapy. METHODS: One hundred eighty-three patients from a university-based rheumatology clinic who were taking MTX completed an initial knowledge questionnaire concerning the proper use and possible toxicity of MTX. Following completion, a nurse reviewed the correct answers with each patient and provided written information on MTX. One hundred thirty-eight of these patients completed a followup questionnaire at the next visit or by mail. The questionnaires were analyzed, and a total MTX knowledge score was calculated. RESULTS: MTX knowledge improved significantly between questionnaires; mean total score (+/- SD) increased from 7.32 +/- 3.99 to 10.23 +/- 3.29 (P < 0.001). After accounting for a person's initial questionnaire score, the addition of a supplemental "MTX pocket-card" was associated with a higher score on the follow-up questionnaire (adjusted odds ration [OR] = 2.37; 95% confidence interval [CI] 1.14, 4.95; P = 0.021). Patients over age 55 were 4 times more likely to have a poorer score compared with patients under age 45 (adjusted OR = 0.23; 95% CI 0.07, 0.73; P = 0.013). CONCLUSION: Knowledge of the toxicity and safe use of MTX was significantly improved by a patient education program utilizing a rheumatology nurse. Older individuals appear to be at higher risk for knowledge deficits. A supplemental MTX pocket-card proved to be a simple but beneficial addition to our MTX educational program.