The seventh-seeded 76ers had pulled off a surprising 90-86 victory Sunday in the series opener after bouncing back from a 13-point halftime deficit.
In Game 2, Detroit, the East's No. 2 seed, grabbed a 25-18 lead after the first period, expanded it to 53-36 at the half and coasted home.
Hamilton added seven rebounds and seven assists, McDyess had 12 rebounds and Wallace seven.
The 76ers' leading scorer, Andre Iguodala, was held to four points after making only one of nine field goal attempts.
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