Vascularization of many solid tumors occurs in vivo as a consequence of the vectorial growth of host capillary endothelial cells along a concentration gradient of a tumor-produced, diffusible angiogenesis factor (AF). Our studies of this process will primarily employ an in vitro model system that has permitted examination of the effects of tumor-derived agents on the growth of cultured endothelial cells (from fetal bovine aorta). The specific objectives of these proposed studies are: 1) to complete studies on the structure determination of a low molecular weight AF from the Walker 256 rat tumor; 2) to conduct, using techniques developed from the Walker tumor studies, a comparative survey on the angiogenic activity and AF molecule(s) present in a variety of tumors that in situ differ in vascularization; 3) to perform a similar survey on the angiogenic properties of homogenates from normal tissues and of dailysates (ultrafiltrates) from animal sera, including sera from tumor-bearing animals; 4) to purify and characterize for comparison AF from other animal tumor tissue, from normal tissues, and from serum (only if the procedures appear to be straightforward as judged from the results with the Walker tumor AF; 5) to examine in a cell culture system the factors affecting the synthesis and release of a tumor AF; 6) to develop, using a rat model system, a new in vivo assay for angiogeneis and antiagiogenesis; and, 7) to employ this bioassay in studies on potential antiangiogenic agents that have been discovered using our in vitro assay. Through our efforts to better understand tumor vascularization in terms of stimulatory and inhibitory cell growth factors we hope to provide means for controlling tumor growth and spread.