Fourteen patients with Lyme disease showed typical clinical features of erythema chronicum migrans. Eighteen biopsy specimens in all were obtained from the cutaneous lesions of these patients. The predominant histologic finding was a superficial and deep perivascular and interstitial infiltrate composed mostly of lymphocytes, or lymphocytes and either plasma cells and eosinophils or both. The plasma cells were found most frequently in biopsy specimens taken from the peripheries of the lesions, whereas eosinophils were found mostly in the centers of lesions. With the Warthin-Starry silver stain, spirochetes were found mostly at the borders of the lesions an in biopsy specimens containing plasma cells. Spirochetes were subsequently cultured from a typical skin lesion of erythema chronicum migrans. These findings corroborate previous indirect evidence that a spirochete might be the cause of Lyme disease.