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Users need to have direct access to sub-navigation but the amount of screen estate for navigation is limited .
Combine horizontal navigation with a sub-menu that flies-out when the users hovers over the main menu-item
For experienced users who want quick access to menu items. Typically there is a main page and all clickable items are grouped under a label. The menu items themselves do not link to a page. Space for navigation is limited, if not consider other navigation systems such as a Directory Navigation. Menu items should be found always in the same spot. The number of mouse-clicks should be minimized. No reload of pages is necessary.
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Fly-out menus can work well but they may also kill usability. The actual implementation is crucial for its success. On the one hand, fly-out menus save space that may be used better for the content area of the site. But on the other hand it hides the navigation from first sight. It is a kind of 'mystery-meat navigation'. If executed well it provides very quick access to sections in the site without cluttering up the screen estate with navigation. When users become accustomed to the fly-out menu, its advantages will prove quite useful. On the other hand, for one-off interactions it may cause usability issues.
On mouse-over show the menu. The menu always directly moves up, down or right (never left) in such a way that it does not cover the other menu items. The flying-out should be instant or very quick otherwise users cannot switch quickly. Preferable combined with a Breadcrumbs. The fly-out menu may exist horizontally or vertically.