Two cases of Whipple's disease were followed by electron microscopic study of periodic peroral suction biopsy specimens of small intestine to show the presence and disappearance of the interstitial lamina proprial organisms, the sequential changes of the macrophages, and the return to normal leukocytic population of the lamina propria following prolonged treatment with tetracycline. The value of electron microscopy in the detection of small numbers of micro-organisms is demonstrated. Ultrastructural study is the most efficient method of demonstrating the presence of diagnostic micro-organisms, measuring the adequacy of treatment, and identifying possible early reactivation of infection.