Since 1950, several investigators have demonstrated that interstitial hypertension is a pathophysiological characteristic of experimental solid tumors. To date, interstitial fluid pressure (IFP) has not been measured in human tumors in situ. In this study we measured with the wick-in-needle technique the interstitial fluid pressure in superficial melanoma metastases (n = 12) in patients (n = 10) before and during systemic therapy. In the majority of tumors the pressure was found to be almost uniform, while in others it varied severalfold. The large variations in IFP in some tumors may be due to technical or biological factors. With the data obtained before and during therapy grouped, the mean IFP in melanoma lesions varied between 2 and 41 mm Hg with an overall mean of 14.3 +/- 12.5 (SD). IFP was found to be significantly higher (P less than 0.01) in large (22.8 +/- 13 mm Hg; n = 6) than in small (5.8 +/- 2mm Hg; n = 6) lesions. This study demonstrates that IFP can be measured in human tumors using the wick-in-needle technique and that the pressure in some of the large melanomas exceeds the values measured to date in rodent tumors or human tumor xenografts. The latter result suggests that caution must be exercised in extrapolating values of pathophysiological parameters from transplanted tumors to human tumors.