Microcantilevers have been used over the last decade to detect biomolecules from solution. Specific binding events on one surface of the microcantilever create a differential stress, resulting in measurable deflection. Here we use this principle to detect human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) gp120 from solution. We observed deflections approximately twice that of the baseline (in PBS) upon specific binding of gp120 to cantilevers decorated on one side with monoclonal antibodies (mAbs) A32 or T8. Subsequent incubation with mAb 17b (known to bind an A32-induced epitope on gp120) further increased deflection of A32- but not T8-presenting cantilevers. This work shows the capability of microcantilever deflection sensors to detect an induced-fit interaction at test concentrations of 8 microg/mL gp120 and 0.17 mg/mL 17b. Further development of this technique could lead to a portable, low-cost device for the effective detection of HIV-1.