The feasibility of using air-cooling to improve the thermal penetration of direct-coupled interstitial ultrasound (US) applicators was investigated using biothermal simulations, bench experiments, phantom testing, and in vivo thermal dosimetry. Two applicator configurations using tubular US transducers were constructed and tested. The first design, intended for simultaneous thermobrachy-therapy, utilizes a 2.5 mm OD transducer with a central lumen to accommodate a radiation source from remote afterloaders. The second applicator consists of a 2.2 mm OD transducer designed for coagulative thermal therapy. Both designs provide cooling of the inner transducer surface by the counterflow of chilled air or CO2 gas through the annulus of the enclosed applicator. The average convective heat transfer (ha) associated with each applicator was determined empirically from curve-fits of radial steady-state temperatures measured in a tissue-mimicking phantom. High levels of convective heat transfer (ha > 500 W m-2 degrees C-1) were demonstrated in both designs at relatively low flow rates (< 5 L min-1). Transient and steady-state radial heating profiles were also measured in vivo (pig thigh muscle) with and without cooling. The therapeutic radius for hyperthermia (41-45 degrees C) was extended from 5-6 mm (without cooling) to 11-19 mm with air-cooling (4.8 L min-1, airflow 10 degrees C), effectively doubling and tripling the thermal penetration in vivo. Similar improvements were demonstrated at higher temperatures with the thermal coagulation applicator. Biothermal simulations, which modeled the physical, thermal, and acoustic parameters of the air-cooled applicator and surrounding tissue, were also used to investigate potential improvements in heating patterns. The simulated radial heating profiles with transducer cooling demonstrated significantly enhanced thermal penetration over the experimental range of convective transfer, and also agreed with in vivo results. These theoretical and experimental results clearly show air-cooling controls the transducer surface temperature, significantly increases thermal penetration, and produces a greater treatment volume for direct-coupled US applicators in hyperthermia and thermal coagulation.