Microvascular permeability of macromolecules in normal and tumor tissues was measured under hyperthermic conditions. Fluorescein-isothiocyanate tagged dextran (150,000 molecular weight) was chosen as a tracer substance. The modified Sandison type rabbit ear chamber was used to study transport in normal (mature granulation) tissue and tumor (VX2 carcinoma) tissue. Hyperthermia (43 degrees C and 50 degrees C for one hour) was induced with a precision thermal water bath attached to the chamber. When heated to 43 degrees C, the normal tissue microvascular permeability increased to 9.4 +/- 7.3 X 10(-8) cm/s, but not statistically different from the control value of 7.3 +/- 3.3 X 10(-8) cm/s. When heated to 50 degrees C, the normal tissue microvascular permeability rose about six-fold to 44.4 +/- 35.3 X 10(-8) cm/s (p less than 0.01). When heated to 43 degrees C, the tumor microvascular permeability increased to 89.4 +/- 29.7 X 10(-8) cm/s, but not statistically different from the control value of 57.3 +/- 39.2 X 10(-8) cm/s. However, when the tumor tissue was heated to 50 degrees C, its permeability nearly doubled to 112.2 +/- 20.8 X 10(-8) cm/s (p less than 0.025).