The effects of i.p. versus i.v. glucose administration on laser Doppler flow (LDF) were studied in peripheral tissue areas of murine FSaII tumors implanted s.c. in the hind foot dorsum and in normal skin of conscious C3Hf/Sed mice. LDF was monitored prior to and continuously for 90 min following the administration of glucose, galactose, or mannitol at doses of 5 or 10 mg/g. Results showed that i.p. administration of hyperosmolar solutions was followed by a substantial, dose-dependent flow reduction which was indistinguishable for the various agents at equal osmotic load, and similar in tumor tissue and normal skin. Reductions in LDF are, therefore, primarily caused by hypovolemic hemoconcentration following i.p. administration of hyperosmolar sugar solutions. In contrast, i.v. administration of these solutions at 5 mg/g caused an initial flow increase (most probably due to a transient hypervolemic hemodilution), with a return to baseline readings within 5-10 min. At 10 mg/g i.v., a biphasic change in LDF occurred with an initial, temporary increase and a significant decline thereafter with no recovery within the observation period. This drop in LDF most probably is due to a decrease in cardiac output and an increase in viscous resistance to flow. Since comparable changes were observed with all agents and in both tissues investigated, it is concluded that the alterations in flow pattern following injection of hyperosmolar solutions are neither glucose nor tissue specific. Glucose- or tumor-specific effects, if present at all, must be of secondary importance in the animal model chosen.