There is conclusive evidence that nonsteroidal anti-inflammatory drugs can increase serum lithium levels, diminish renal lithium clearance, and possibly induce lithium toxicity. Such an interaction has occurred in patients with normal renal function. The effect on serum lithium levels varies greatly among different nonsteroidal anti-inflammatory drugs, indomethacin seeming most potent. On the other hand, there is no convincing evidence that sulindac and aspirin affect serum lithium levels to a clinically significant degree. Ibuprofen and naproxen can significantly increase serum lithium levels, but there is marked interindividual variation. Patients receiving nonsteroidal anti-inflammatory drugs must have their serum lithium levels checked every 4-5 days until the extent of drug interaction is assessed. A reduction in lithium dosage may be needed in some cases.