Bromopyrrole alkaloids are a typical class of marine natural products, commonly occurring as secondary metabolites of various marine sponges. In studies on bioactive substances from Okinawan marine organisms, the authors previously isolated several bromopyrrole alkaloids with pharmacological utility (e.g., α-adrenoceptor blockers, serotonergic receptor antagonists, actomyosin ATPase activators). Recently, they examined the bioactive constituents of the Okinawan sponge Hymeniacidon sp. and isolated three novel compounds, manzacidins A-C (1-3), which represent an unprecedented class of bromopyrrole alkaloids featuring an unusual 3,4,5,6-tetrahydropyrimidine ring. This work describes the isolation and structure elucidation of these compounds. The sponge was extracted with methanol, and the extract was partitioned and purified via silica gel flash chromatography and reversed-phase HPLC to yield manzacidins A-C as colorless oils. Manzacidin A (1) was structurally characterized using UV, IR, FABMS, HRFABMS, and multi-dimensional NMR techniques (DEPT, 1H-1H COSY, HMQC, HMBC, NOE), revealing a 3-bromopyrrole-5-carboxylic acid moiety linked to a 3,4,5,6-tetrahydro-4-(hydroxymethyl)-4-methyl-6-pyrimidinecarboxylic acid unit. Manzacidin B (2) is an oxygenated derivative of 1, and manzacidin C (3) is a C-11 stereoisomer of 1. Manzacidins A-C are the first bromopyrrole alkaloids with a tetrahydropyrimidine ring connected via an ester bond and the first such compounds from marine sources. Biosynthetically, the tetrahydropyrimidine ring may arise from the condensation of formic acid with an unusual amino acid like γ-amino-δ-hydroxyleucine.