Sorbitan fatty acid eaters (Spans) and the corresponding polyoxyethylene (POE) adducts (Tweens) have a wide range of applications in the pharmaceutical and other industries. In some formulations, mixtures of Span surfactants and Tween surfactants are required, but some of the physical properties of these mixtures are not well defined. To assess the mixing behavior of Spans and Tweens, selected mixtures of these surfactants were studied using Langmuir compression isotherms. Our data indicate that mixtures of Tween 80 (polyoxyethylene sorbitan monoleate) with Span 80 (sorbitan monooleate), Span 83 (sorbitan sesquioleate), or Span 85 (sorbitan trioleate) form expanded mixed monolayer films at the planar air-water interface. Mixing of Tween 80 with these three Spans exhibits significant repulsive nonideality except at low proportions of Tween 80 in Span 85. A model to explain the observed phase behavior is proposed.