Newly engorged nymphs of the lone star tick, Amblyomma americanum (L.), were continuously exposed to 4 μg/cm² of pyriproxyfen residues in glass vials. Treatment of engorged nymphs (n = 285) resulted in significant molting inhibition, with more than one-fourth (26.7%, n = 76) of nymphs dying before or during ecdysis. Treatment effects were evident among ticks that molted to the adult stage, with 26.7% (n = 76) of females, and 17.9% (n = 51) of males exhibiting moribund physical characteristics (i.e., lethargy; dull, discolored and desiccated cuticles; lacking full locomotor competency). A few molted adult ticks (10 males, four females) were dead upon inspection. Only 11.2% of pyriproxyfen treated, emergent females (n = 32), and 11.5% of treated emergent males (n = 25) from 285 ticks treated as engorged nymphs, exhibited “normal” physical appearance and possessed a full range of locomotor activity. Treated adult ticks maintained within a desiccating environmental chamber at 0% RH and 23°C, had significantly accelerated whole-body water loss rates in comparison to untreated males and females maintained under the same environmental conditions. Additionally, treated adult ticks maintained under optimal environmental conditions (23°C and >95% RH) sustained 100% mortality within 32 d following assignment to these conditions (or 79 d posttreatment as engorged nymphs), whereas untreated ticks had 0% mortality for the same duration of time. Results demonstrate that continuous exposure of nymphs to pyriproxyfen disrupted molting, and accelerated both whole-body water loss and subsequent mortality among emergent adult ticks.