Receptor tyrosine kinases (RTKs) are membrane proteins that regulate cell growth, proliferation, and differentiation. Aberrant RTK signaling is at the heart of many diseases connected to development and growth. For example, mutations of the epidermal growth factor receptor (EGFR or ErbB1) are linked to tumorigenesis, most notably in lung cancer, for which several FDA-approved EGFR inhibitors have been developed. Lateral contacts between RTKs in the plasma membrane have a direct effect on their phosphorylation state and enzymatic activity. This spatial regulation is linked to cellular function, but it is challenging to resolve in the complex environment of the plasma membrane. In my lab we develop fluorescence assays to measure membrane protein interactions in situ. Pulsed interleaved excitation fluorescence cross-correlation spectroscopy (PIE-FCCS) has been especially powerful because it is sensitive to protein mobility, concentration, and monomer/dimer/oligomer distributions. In this talk, I will describe ongoing work in my group to investigate the spatial regulation of two RTKS, EGFR and EphA2.