1. Segments ofAedes aegypti Malpighian tubules were isolated and perfused with symmetrical solutions, and the transepithelial electrical potential difference (Vt) and resistance (Rt) were determined. 2. Vt avaraged 53±3 (110) mV lumen positive (mean±SE, number of tubules), and was inhibited by dinitrophenol, but not by amiloride, furosemide, or ouabain (all added to the serosal medium). Rt averaged 21±4(15) kohmcm. 3. Following treatment with the secretagogue dibutyryl cAMP (1 mM), Vt increased to 99±8(9) mV and Rt dropped to, 14±6(6) kohm·cm. Effects of cAMP were reversible and dependent upon serosal [Na]. 4. Treatment with another secretagogue, an extract of mosquito heads (0.1 head/μl), caused Vt to drop to 1±1(8) mV and Rt to fall to 9±3(7) kohm·cm. These effects were also reversible, but they were dependent upon serosal [Cl]. 5. Since previous studies showed that cAMP stimulates secretion of Na in these tubules, it is concluded that cAMP stimulates active Na transport that is responsible for the observed increase in Vt. 6. Head extract apparently stimulates the active secretion of K, but the dependence of the head extract effects on Cl, combined with the low Vt seen during head extract treatment, suggests that the secretion of K, and perhaps also of Na, is directly or indirectly coupled to Cl secretion, yielding neutral transport of electrolytes and consequently low values of Vt