Severe adverse effects of low-dose methotrexate (less than 20 mg per week) are believed to be rare. We report eight cases of severe tricytopenia or pancytopenia seen in two medical departments of the same hospital in patients receiving low-dose methotrexate. Three patients had been under methotrexate for less than one month. Of the six patients with joint disease, five had rheumatoid arthritis and one psoriatic arthritis. A review of the literature found 92 previously reported cases of severe tricytopenia or pancytopenia induced by low-dose methotrexate. Of the total of 100 cases, 24 were fatal and 25 occurred within one month of treatment initiation. Potential risk factors were identifiable retrospectively in at least 50% of cases but were not all predictable or present at treatment initiation. In 30% of cases, no explanation for the hematologic complication was found, and in an additional 20% missing data precluded definite conclusions. The role of the risk factors incriminated in the literature is discussed. Although infrequent, cytopenia is a severe complication of methotrexate therapy that warrants a number of precautions, including periodic creatinine clearance and serum albumin determinations. Furthermore, the weekly dosing schedule should be printed on methotrexate boxes.