Thesis (MSc. ARST) North-West University, Mafikeng Campus, 2003 Cancer therapy with high-energy particles has proved to be beneficial over the last 10 years. Protons are regarded as being more advantageous because of their distinctive physical depth dose distribution that allows dose conformation to the tumor while sparing normal tissue. In this study, the relative biological effectiveness (RBE) values for the 200-MeV clinical proton beam at iThemba LABS were measured at strategic positions along a 5 cm Spread-Out-Bragg-Peak (SOBP). RBE values were evaluated at the initial plateau of the virgin beam (24.2 mm in Perspex), and at the middle part, distal part and distal edge (12.4% max. dose) along the SOBP (depth in Perspex= 161.4, 181.3 and 207.7 mm respectively). Biological systems used were Chinese hamster ovary cells (CHO-Kl) for both cell survival and micronuclei frequencies as well as human T-lymphocytes for micronuclei frequency analysis. (60)^Co y-irradiation served as a reference. Cell survival measurements yielded RBE values of 1.17 at the distal part and 1.62 at the distal edge (12.4 max. dose). For micronuclei analysis, a limiting RBEap+ay value of 1.3 at the distal part was observed. Using T-lymphocytes, RBEap+/ay values calculated were 2.1, 2.7 and 3.2 at the middle part, distal part and distal edge, respectively. These results show an increase in RBE with depth of penetration and are explained by an increase in ionization density at the end of the SOBP. This is influenced by a high fraction of low-energy protons at that position. Protons were found to be most potent per unit dose towards the end as they slow down to a complete stop. It is recommended that an RBE value slightly greater than the current 1.1 be applied in therapy. Also, that the less steep biological effective depth dose curve be taken into account when dose planning. Masters