Work involving pipetting is associated with elevated rates of musculoskeletal disorders of the hand and wrist. The purpose of this study was to quantify thumb loading and muscle activity and determine if they varied among pipetting tasks. Fourteen experienced participants performed nine pipetting tasks while surface electromyography was measured for the extensor pollicis brevis, abductor pollicis longus, flexor pollicis longus, and abductor pollicis brevis muscles. For five tasks, participants used a pipette instrumented to measure the thumb force applied to the plunger. High-precision tasks significantly increased static muscle activity but reduced peak thumb force on average 5% as compared with low-precision tasks. Pipetting high-viscosity fluids increased peak thumb forces on average 11% as compared with pipetting low-viscosity fluids. Use of a latch pipette increased muscle activity of three muscles. We conclude that pipette design and pipetting tasks can influence applied thumb force and muscle activity. We recommend that pipettes be designed to limit applied peak forces and that pipette users be instructed in use patterns that will reduce applied forces. Actual or potential applications of this research include modifications to pipette designs and worker training in order to reduce hand pain associated with pipetting.