Previous studies have documented decreased levels of platelet sodium, potassium adenosine triphosphatase (Na+,K+ ATPase) enzyme activity in allergic subjects. The purpose of this study was to determine the effect of several drugs used to treat allergy and asthma on platelet Na+,K+ ATPase activity. Platelets from five allergic and five nonallergic subjects were incubated at 37-degrees-C for 30 minutes with cortisol (1.0 to 3.6 mug/ml), theophylline (10 to 40 mug/ml), cromolyn (0.5 to 2.0 mug/ml), albuterol (3 to 24 ng/ml), chlorpheniramine (2.5 to 20 mug/ml), or diluent. The platelets were then rinsed, sonicated, serially centrifuged, and assayed for Na+,K+ ATPase activity nmol/min x mug protein by spectrophotometry. Mean activity (+/- 1 SEM) for the diluent incubation was 5.55 +/- 1.27 nmol/min x mug protein and 0.91 +/- 0.32 nmol/min x mug protein for the nonallergic and allergic subjects, respectively. The enzyme activity of allergic platelets (same units as above) increased after incubation with the following drugs: cortisol, 6.07 +/- 1.75 (p < 0.025) at 1.0 mug/ml, 7.55 +/- 1.36 (p < 0.005) at 1.4 mug/ml, and 5.95 +/- 0.91 (p < 0.025) at 1.8 mug/ml; cromolyn, 5.79 +/- 1.68 (p < 0.050) at 1.0 mug/ml; and albuterol, 4.43 +/- 1.61 (p < 0.051 at 12 ng/ml. Theophylline and chlorpheniramine did not have a similar effect on Na+,K+ ATPase activity. These data show that some of the drugs commonly used to treat allergic patients, especially anti-inflammatory agents, can increase the depressed platelet levels of Na+,K+ ATPase activity observed in allergic subjects. Modulation of Na+,K+ ATPase is a possible mechanism of action for these drugs in vivo.