Two patients with palindromic rheumatism were diagnosed with Whipple's disease 5 years after onset of the joint symptoms. Twenty-one previously published cases of Whipple's disease with palindromic rheumatism as the first manifestation were identified. Statistically significant differences were found between palindromic rheumatism in patients with and without Whipple's disease. Patients with Whipple's disease were more likely to be male and to exhibit fever and elevated erythrocyte sedimentation rates during joint symptom flares, whereas they were less likely to have involvement of the metacarpophalangeal and proximal interphalangeal joints. None of the patients with Whipple's disease had either skin manifestations of palindromic rheumatism (nodules or paraarthritis) or positive tests for rheumatoid factor. Patients with palindromic rheumatism exhibiting these features should have an intestinal biopsy to look for Whipple's disease.