PURPOSE: To (a) determine the appearances and timing of heterogeneous splenic enhancement at spiral computed tomography (CT) and (b) identify variables influencing heterogeneous splenic enhancement. MATERIALS AND METHODS: Sequential isolevel (24-mAs) CT images of the spleen obtained at 6-second intervals after initiation of contrast material injection in 112 children (mean age, 4.5 years) were reviewed. Heterogeneity characteristics assessed included type, onset, maximum, and resolution. Relationship to variables (injection rate, age, splenomegaly) was assessed with the Fisher exact test. RESULTS: Eighty-one of the 112 patients (72%) had transient heterogeneity: archiform (45 patients), diffuse (25 patients), and focal (11 patients). Mean times were as follows: initial visualization after onset of contrast material injection, 19.2 seconds; maximum heterogeneity, 27.3 seconds; and resolution, 47.4 seconds. Statistically significant relationships were seen between frequency of heterogeneity and injection rate (> or = 1 mL/sec, 82%; < 1 mL/sec, 50% [P = .001]), age (> 1 year, 76%; < or = 1 year, 46% [P = .04]), and splenomegaly (present, 20%; absent, 77% [P = .048]). CONCLUSION: Heterogeneous splenic contrast enhancement is common, has several patterns of appearance, and is predictably encountered during the 70 seconds after the initiation of contrast material injection. Injection rate, age, and presence of splenic disease influence the frequency with which these artifacts are encountered.