Serum lithium levels are known to rise dramatically during concurrent administration with nonsteroidal antiinflammatory drugs (NSAIDs). A lithium-sparing effect of the NSAID sulindac is reported here. Two cases are presented in which sulindac antirheumatic therapy was commenced during stabilized lithium treatment for recurrent endogenous depression. Elevation of serum lithium levels due to sulindac was not seen. Serum lithium levels paradoxically dropped below the recognized therapeutic range shortly after sulindac introduction, subsequently returning to baseline levels without overall loss of therapeutic control. It is suggested that these two drugs may be used together when control of arthritic symptoms is necessary for patients taking lithium. However, no change should be made to lithium dosage during the drop phase, to avoid marked fluctuations in serum lithium levels. Conflicting evidence in the current literature highlights the need for more investigation into this lithium-sparing effect of sulindac.