Background: Procedural learning refers to rule-based motor skill learning and storage. It involves the cerebellum, striatum and motor areas of the frontal lobe network. Fragile X syndrome, which has been linked with anatomical abnormalities within the striatum, may result in implicit procedural learning deficit. Methods: To address this issue, a serial reaction time (RT) task including six blocks of trials was performed by 14 individuals with fragile X syndrome, 12 individuals with Down syndrome and 12 mental age-matched control subjects. The first (B1) and fifth (B5) blocks were random whereas the others (B2, B3, B4 and B6) consisted of a repeated 10-step sequence. Results were analysed by Kruskal-Wallis one-way analysis of variance and Wilcoxon signed-rank test. Results: For patients with fragile X syndrome, the RT was highly suggestive of preserved implicit learning as a significant difference was observed between blocks B5 and B6 (P = 0.009). However, the difference of RT between B4 and B5 did not reach significance, possibly due to a subgroup of individuals who did not learn. In contrast, in the Down syndrome group, RT decreased significantly between B4 and B5 (W = 2; P = 0.003) but not between the last ordered block (B6) and the last random block (B5), suggesting a weakness in procedural learning which was sensitive to the interfering random block. Conclusion: Implicit learning is variable in genetic syndromes and therefore relatively independent of general intellectual capacities. The results are discussed together with previous reports.