23 young adult males with Reiter''s syndrome were studied. The frequent involvement of the skin and mucous membranes is emphasized. The skin lesions may mimic those of keratoderma blennorrhagica. The arthritis was prolonged in duration but rarely produced permanent deformity. Apparently the disease may be due to a venereal infection, with the urethra as the portal of entry. Bacteriologic and serologic studies demonstrated active gonococcal infection in only one of the 23 cases. Pleuropneumonia-like organisms were isolated from the urethral exudate in only 1 of 8 patients examined. Fecal cultures in 5 patients with diarrhea failed to show Shigella or other bacterial pathogens. The etiology remains in doubt. The most effective therapeutic measures were rest, high caloric diets, salicylates for pain and intensive physiotherapy. Streptomycin seemed to produce slight improvement in 4 of 6 patients. Cortisone and pituitary adrenocorticotropin (ACTH) caused a temporary decrease in the fever and arthritis of a few patients.