The injectable anesthetic etomidate and a clip that facilitates hyperthermia by water bath immersion (the "Gibbs clip") were evaluated for their suitability with subcutaneous flank RIF-1 tumors in C3H/HeJ mice. For tumors between 100 and 250 mg (mean, 160 mg), etomidate at 40 mg kg-1 ip did not significantly increase the radiobiologic hypoxic fraction (RHF); as calculated from an in vitro assay after treatment in vivo the RHF increased from 0.06 (95% C.I.:0.03-0.13) to 0.08 (0.04-0.16). In contrast, for larger tumors (270-650 mg; mean, 400 mg) etomidate increased the RHF from 0.08 (0.04-0.17) to 0.28 (0.14-0.60). Holding 250-mg-or-less tumors 3-mm laterally away from the flank in an X-ray jig did not significantly reduce tumor blood flow as inferred from the clearance rates of Xe, but the RHF of 0.15 (0.08-0.26) was significantly (P less than 0.05) greater than the RHF in unanesthetized mice, although not the RHF in anesthetized mice. The Gibbs clip, which folded skin around a tumor to enhance thermal conduction from a water bath, did not impair the increase in tumor blood flow in response to the cardiovascular arousal associated with exposure to a hyperthermic stimulus. Intratumor temperature was within 0.25 degrees C of bath temperature 3 min after the tumor and clip were immersed, but only when rectal temperatures were at 37 degrees C or above; tumor blood flow increased intratumor temperature gradients by 0.10 degrees C for each 1.5 degrees C that the body temperature was below 37 degrees C.