The following N-(alpha-hydroxylakanoyl) derivatives of Leu-Val-Phe-OCH3 were synthesized and tested for their ability to inhibit human amniotic renin: D- and L-alpha-hydroxyisocaproyl-Leu-Val-Phe-OCH3, D- and L-alpha-hydroxyisovaleryl-Leu-Val-Phe-OCH3, L-2-hydroxy-3-phenylpropanoyl-Leu-Val-Phe-OCH3, and D- and L-alpha-hydroxyphenylacetyl-Leu-Val-Phe-OCH3. Analysis of the compounds through the use of Dixion plots showed all of the compounds to be competitive inhibitors of renin. All but D-alpha-hydroxyisovaleryl-Leu-Val-Phe-OCH3 were found to be more active than the known tetrapeptide inhibitor Leu-Leu-Val-Phe-OCH3 (1). The two most active compounds of the series were L-alpha-hydroxyisocaproyl-Leu-Val-Phe-OCH3 (Ki = 0.23 mM) and L-alpha-hydroxyisovaleryl-Leu-Val-Phe-OCH3 (Ki = 0.3 mM).