EGF (epiderma growth factor) has been chemically modified to give nitrated, acetylated, and methylated derivatives. It has also been cleaved, both chemically (CNBr) and enzymatically to give EGF analogs, all of which have been tested for EGF receptor competition and for mitogenic activity. We have synthesized a series of overlapping fragments of mouse EGF. Biological assays of these fragments suggest that the 14-31 region of EGF is most important for binding. Enzymatic resynthesis of proteins is being investigated with the object of synthesizing EGF analogs by enzymatic condensation of an appropriate peptide with an EGF fragment obtained from enzymatic degredation of native EGF. In collaboration with units listed above, we are undertaking x-ray structural studies of EGF. Using computer graphics, a modeled EGF tertiary structure was derived.