Handrim wheelchair propulsion is a straining form of ambulation. In contrast, arm crank exercise in laboratory settings has shown a higher degree of gross mechanical efficiency and increased levels of peak power output. Moreover, arm crank exercise can be conducted at different gear ratios and in asynchronic or synchronic mode. Although tricycle crank exercise or handcycling has become increasingly popular for recreational use, sports and outdoor wheeling over the last decade, today little is known about the cardiopulmonary strain in handcycling. The physiological and subjective responses during handcycling were evaluated in a group of 12 male non-wheelchair users (age 24.6±2.7 yr; body weight 73.7± 9.7 kg). During an incremental submaximal exercise test on a motor driven treadmill (velocity: 1.8 ms-1; an incremental slope of 1% per 3 min; 0-3%; mean power output of the subject group varied between 7.6±1.6 W and 47.5±6.2 W), effects of asynchronic and synchronic crank settings and three different gear ratios (1: 0.42, 1:0.59, 1:0.741 (or 24, 36 and 44 rpm)) were evaluated in a random testing sequence. Significantly lower levels of mean oxygen uptake, ventilation, relative heart rate and oxygen uptake were seen during synchronic arm use and for the lighter gear ratios (i.e. higher movement frequency; 44 rpm). Subjective local perceived discomfort showed similar trends. Conversely, gross mechanical efficiency appeared higher for these conditions. The need for strong medio-lateral stabilizing muscle effort during asynchronic arm use (to ensure a proper wheeling direction as well as simultaneous power transfer to the cranks) and the effective use of the trunk in this subject group may explain the advantage of synchronic arm use. Whether this advantage is consolidated among wheelchair confined individuals needs further study. Apart from the important effects of a shift in force-velocity characteristics of the contracting muscles with varying gear ratios, increased static finger flexor and arm muscle activity may explain the increased strain in the somewhat unnatural heavy gear condition (24 rpm) at the studied velocity. Results need to be re-evaluated for wheelchair user populations and different higher velocities and power conditions. Moreover, other aspects of the wheelchair-user interface must be studied in order to generate optimum fitting and design guidelines for different user groups and conditions of use.