To review and compare the risks of nonnarcotic analgesic toxicities in adults and estimate the relative healthcare costs of these toxicities, since direct comparison of costs is not possible. A MEDLINE search of the literature from 1969 to 1995 was used to identify pertinent data. Additional references were identified from articles obtained in the search. Information was obtained from prospective, retrospective, controlled, and uncontrolled studies; case reports; and review articles. Estimates of annual US costs of toxicities were extrapolated and synthesized from data from diagnosis-related groups, published information about the incidence of toxicity, or local data. Chronic use of nonsteroidal antiinflammatory drugs (NSAIDs) is associated with a high incidence of acute renal toxicity and gastrointestinal toxicity. The most common problems associated with acetaminophen use are hepatoxicity after acute problems ingestion of large doses (> 10 g) or habitual use of smaller doses (< 4 g), particularly in alcoholic patients, and chronic analgesic nephropathy. Aspirin use is associated with a high incidence of gastrointestinal and acute renal toxicity in certain patient groups. Available data suggest that acetaminophen, used intermittently, remains the nonnarcotic analgesic of choice in many patient populations, including those with impaired renal function, gastrointestinal disease, and bleeding disorders. Estimated annual US costs associated with the toxicities of acetaminophen (excluding hepatotoxicity), aspirin (acute upper gastrointestinal bleeding only), and NSAIDs (excluding non-upper gastrointestinal hemorrhagic complications and hepatotoxicity) are about $51.5 million, $358.6 million, and $1.35 billion, respectively. Intermittent use of most nonnarcotic analgesics produces a small risk of chronic renal or hepatic toxicity. Gastrointestinal toxicity, especially upper gastrointestinal bleeding, remains a significant problem with NSAIDs and aspirin. Acetaminophen remains the nonnarcotic analgesic of choice for intermittent use by most patient groups. The toxicities associated with NSAIDs constitute about 72.6% of the total toxicities (costs $1.86 billion) caused by NSAIDs, acetaminophen, and aspirin.