We examined the effectiveness of the Tzanck preparation compared with viral isolation in 32 lesions of cutaneous herpes simplex infection in 30 consecutive patients. Seventy-eight percent had positive cultures, even though the clinical history and lesion morphological findings were typical in all situations. Other authors have also noted that viral isolation does not reach 100% even in the face of typical clinical history. Fifty-three percent of the Tzanck smears were positive. These preparations had a high correlation with positive viral cultures (94.1%). Vesicles were more likely to yield a positive culture than Tzanck smear (100% and 66.7%, respectively). Pustules yielded positive cultures in 72.8% and positive Tzanck smears in 54.5%, while crusted-ulcer lesions were usually not positive by either technique (34%, 16%). A positive Tzanck preparation is an accurate, rapid tool for the diagnosis of cutaneous herpes simplex.