We address a new variant of the hybrid flow shop problem (HFSP) taking into consideration machine blocking, both sequence-independent and sequence-dependent setup times, as well as unrelated parallel machines per stage. Two mixed integer programming models are proposed for the variants under study. After preliminary computational experiments, the need for a heuristic algorithm was identified. We propose a reactive GRASP for the aforementioned variants. Computational experiments are carried out on synthetic problem instances to test the performance of the proposed models and algorithm. The objective function adopted is the minimization of the makespan with the relative deviation as a performance criterion. The results indicate superiority of the proposed reactive GRASP in comparison with an exact algorithm implemented in a commercial solver used to solve the mixed integer programming models.