The effect of formulation factors on the steady-state flux of hydrocortisone through mouse skin was evaluated. The flux of hydrocortisone from solutions containing propylene glycol as a cosolvent varied inversely with the propylene glycol concentration. Solutions containing 2-propanol gave flux values higher than those obtained from propylene glycol solutions and independent of the 2-propanol concentration. Addition of polysorbate 80 to 2-propanol–water solutions produced an increase in flux at low surfactant concentrations that reached an apparent limiting value at higher concentrations. The penetration flux was the same from solutions and gels. The role of vehicle–skin interactions in penetration is emphasized.