For more than 30 years nitrofurantoin has been a widely prescribed and effective agent in the treatment of urinary tract infections. During this time, it has withstood the rigors of constant clinical evaluation and has competed successfully with more recent antibacterial agents. As with many widely used drugs, some serious and potentially hazardous reactions to therapy have been documented. This article reviews and analyzes major reported reactions and interactions from both published and unpublished sources. Incidence rates have been calculated for pulmonary, hepatic, neurological, and hematological responses. Calculated rates of occurrence were very low, and ranged from 0.001 percent of courses of therapy (all types of pulmonary reactions combined) to 0.0007 percent (neurological reactions). Reports on interactions of nitrofurantoin with alcohol, antacids, and oral contraceptives are unfounded and anecdotal. Interactions with nalidixic and oxolinic acids are not clinically significant, and only one case of interaction has been reported with phenytoin. Bioavailability is enhanced by food or propantheline. False positives occur with Benedict's test for urine glucose estimations.